tbuckley/cabot-search huggingface dataset:
Minimally invasive approaches for the early detection of endometrial cancer
Authors: Yufei Shen, Wenqing Yang, Jiachen Liu, Yu Zhang
Journal: Molecular Cancer (2023)

Endometrial cancer (EC) is one of the most common gynecologic cancers and its incidence is rising globally. Although advanced EC has a poor prognosis; diagnosing EC at an earlier stage could improve long-term patient outcomes. However, there is no consensus on the early detection strategies for EC and the current diagnostic practices such as transvaginal ultrasound, hysteroscopy and endometrial biopsy are invasive, costly and low in specificity. Thus, accurate and less invasive screening tests that detect EC in women with early stages of the disease are needed. Current research has revolutionized novel EC early detection methodologies in many aspects. This review aims to comprehensively characterizes minimally invasive screening techniques that can be applied to EC in the future, and fully demonstrate their potential in the early detection of EC.
spSeudoMap: cell type mapping of spatial transcriptomics using unmatched single-cell RNA-seq data
Authors: Sungwoo Bae, Hongyoon Choi, Dong Soo Lee
Journal: Genome Medicine (2023)

Abstract Since many single-cell RNA-seq (scRNA-seq) data are obtained after cell sorting, such as when investigating immune cells, tracking cellular landscape by integrating single-cell data with spatial transcriptomic data is limited due to cell type and cell composition mismatch between the two datasets. We developed a method, spSeudoMap, which utilizes sorted scRNA-seq data to create virtual cell mixtures that closely mimic the gene expression of spatial data and trains a domain adaptation model for predicting spatial cell compositions. The method was applied in brain and breast cancer tissues and accurately predicted the topography of cell subpopulations. spSeudoMap may help clarify the roles of a few, but crucial cell types.
Author Correction: Dapagliflozin in heart failure with improved ejection fraction: a prespecified analysis of the DELIVER trial
Authors: Orly Vardeny, James C. Fang, Akshay S. Desai, Pardeep S. Jhund, Brian Claggett, Muthiah Vaduganathan, Rudolf A. de Boer, Adrian F. Hernandez, Carolyn S. P. Lam, Silvio E. Inzucchi, Felipe A. Martinez, Mikhail N. Kosiborod, David DeMets, Eileen O’Meara, Shelley Zieroth, Josep Comin-Colet, Jaroslaw Drozdz, Chern-En Chiang, Masafumi Kitakaze, Magnus Petersson, Daniel Lindholm, Anna Maria Langkilde, John J. V. McMurray, Scott D. Solomon
Journal: Nature Medicine (2023)

In the version of this article initially published, there was an error in the abstract, where in the sentence now reading, in part, "In participants with HFimpEF… first worsening heart failure events (HR = 0.84)," the hazard ratio originally read "0.78," while in the second paragraph of the "Outcomes by HFimpEF status" Results subsection, in the sentence now reading, in part, "The effect of dapagliflozin on HF outcomes was also similar in those with HFimpEF (HR = 0.84, 95% CI = 0.61-1.14)and those with LVEF consistently over 40% (HR = 0.78)," the hazard ratio values were mistakenly interchanged.
Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment
Authors: Josep M. Llovet, Catherine E. Willoughby, Amit G. Singal, Tim F. Greten, Mathias Heikenwälder, Hashem B. El-Serag, Richard S. Finn, Scott L. Friedman
Journal: Nature Reviews Gastroenterology & Hepatology (2023)
Diagnostic classification of childhood cancer using multiscale transcriptomics
Authors: Federico Comitani, Joshua O. Nash, Sarah Cohen-Gogo, Astra I. Chang, Timmy T. Wen, Anant Maheshwari, Bipasha Goyal, Earvin S. Tio, Kevin Tabatabaei, Chelsea Mayoh, Regis Zhao, Ben Ho, Ledia Brunga, John E. G. Lawrence, Petra Balogh, Adrienne M. Flanagan, Sarah Teichmann, Annie Huang, Vijay Ramaswamy, Johann Hitzler, Jonathan D. Wasserman, Rebecca A. Gladdy, Brendan C. Dickson, Uri Tabori, Mark J. Cowley, Sam Behjati, David Malkin, Anita Villani, Meredith S. Irwin, Adam Shlien
Journal: Nature Medicine (2023)

The causes of pediatric cancers' distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types.
A complex microRNA regulatory network may control the HCP5/UTP3/c-Myc/VAMP3 signaling axis
Authors: Ion Cristóbal, Andrea Santos, Federico Rojo, Jesús García-Foncillas
Journal: Molecular Therapy (2023)

The recently published work by Nan and colleagues1 describes the functional impact of the long non-coding RNA (lncRNA) histocompatibility leukocyte antigen complex P5 (HCP5) as an apoptosis inhibitor through the UTP3/c-Myc/VAMP3 signaling axis in esophageal squamous cell carcinoma (ESCC). The authors demonstrated that HCP5 interacts and stabilizes UTP3 small-subunit processome component (UTP3) by affecting E3 ligase tripartite motif containing 29 (TRIM29)-mediated ubiquitination and subsequent proteosome degradation of UTP3.
On Consolidation and Competition — The Trials and Triumphs of Health Care Antitrust Law
Authors: Jaime S. King
Journal: New England Journal of Medicine (2023)

Interview with Prof. Jaime King on the functions of antitrust law and the effects of health care consolidation on prices, quality of care, and access to care. (14:20)Download Consolidation in health care has occurred by means of horizontal, vertical, and cross-market transactions as well as private-equity investment. In recent years, such moves have gone largely unchecked.
Novel Twin‐Crystal Nanosheets with MnO<sub>2</sub> Modification to Combat Bacterial Biofilm against Periodontal Infections via Multipattern Strategies
Authors: Qiuhan Chen, Manlin Qi, Fangyu Shi, Chengyu Liu, Yujia Shi, Yue Sun, Xue Bai, Lin Wang, Xiaolin Sun, Biao Dong, Chunyan Li
Journal: Advanced Healthcare Materials (2023)

Nowadays the multifunctional approaches to kill oral bacteria based on various nanocomposites have made great progress against periodontal infections, while the material structure and its functional integration are still insufficient. Herein, this work proposes a therapeutic strategy of chemodynamical therapy (CDT) and photothermal therapy (PTT) in monocrystals to effectively enhance the synergistic treatment. The CuS/MnS@MnO2 consisting of hexagonal CuS/MnS nano-twin-crystal with a shell layer of MnO2 is developed. In this nanosystem, the purpose of synergistic treatment of periodontitis by combining PTT/CDT is achieved within a CuS/MnS monocrystal, where CuS serves to achieve photothermal conversion, dissipate the biofilm and transfer the heat in situ to the integrated MnS, thus promoting the Mn2+ -mediated CDT process. Meanwhile, the CDT process can generate the highly toxic hydroxyl radical to destroy extracellular DNA by utilization of endogenous H2 O2 produced by Streptococci in the oral biofilm, cooperating with PTT to dissipate the bacterial biofilm. With the design of the outer shell of MnO2 , the selective bacteria-killing can be realized by producing oxygen which can protect the periodontal non-pathogenic aerobic bacteria and threaten the survival of anaerobic pathogens. Therefore, such design via multipattern strategies to combat microorganisms would provide a bright prospect for the clinical treatment of bacterial infections.
Monitoring of Organ Dysfunction in Sepsis/Systemic Inflammatory Response Syndrome
Authors: THEA KOCH, STEFAN GEIGER, MAX J. R. RAGALLER
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Sepsis and systemic inflammatory response syndrome—induced severe disruption of microcirculation and consecutive tissue hypoxia is considered a key factor in the development of organ dysfunction and multiple organ failure. The conventionally measured global variables such as lactate or macrohemodynamic parameters using a pulmonary artery catheter do not adequately mirror microcirculatory disturbances. Evaluation of the severity of microcirculatory distress and the effectiveness of resuscitation strategies requires new clinical technologies aimed at the microcirculation. It is anticipated that novel techniques such as optical spectroscopy and intelligent biosensors will play a major role in the development of new monitoring systems. In general, the current monitoring of organ dysfunction is characterized by a trend from invasive to noninvasive and “safe” techniques, which provide bedside or even on-line monitoring and allow a more precise and earlier detection of organ dysfunction. Techniques for the assessment of regional perfusion and microcirculatory bioenergetics to direct therapeutic procedures are expected to refine and optimize clinical treatment of critically ill patients in the future. This article addresses the question of which variables should be monitored, what is feasible, and what is valid for therapeutic consequences. Recent developments in monitoring of macro- and microcirculation and organ-specific dysfunction, e.g., lung, kidney, are described with respect to their advantages and limitations, and future directions are outlined.
Polycystic disease of the liver
Authors: Gregory T. Everson, Matthew R. G. Taylor, Brian R. Doctor
Journal: Hepatology (2004)

Autosomal dominant polycystic disease is genetically heterogeneous with mutations in two distinct genes predisposing to the combination of renal and liver cysts (AD-PKD1 and AD-PKD2) and mutations in a third gene yielding isolated liver cysts (the polycystic liver disease gene). Transcription and translation of the PKD1 gene produces polycystin-1, an integral membrane protein that may serve as an extracellular receptor. Mutations occur throughout the PKD1 gene, but more severe disease is associated with N-terminal mutations. The PKD2 gene product, polycystin-2, is an integral membrane protein with molecular characteristics of a calcium-permeant cation channel. Mutations occur throughout the PKD2 gene, and severity of disease may vary with site of mutation in PKD2 and the functional consequence on the resultant polycystin-2 protein. Polycystic liver disease is genetically linked to protein kinase C substrate 80K-H (PRKCSH). The PRKCSH gene encodes hepatocystin, a protein that moderates glycosylation and fibroblast growth factor receptor signaling. More prominent in women, hepatic cysts emerge after the onset of puberty and dramatically increase in number and size through the child-bearing years of early and middle adult life. Although liver failure or complications of advanced liver disease are rare, some patients develop massive hepatic cystic disease and become clinically symptomatic. There is no effective medical therapy. Interventional and surgical options include cyst aspiration and sclerosis, open or laparoscopic cyst fenestration, hepatic resection, and liver transplantation. (Hepatology 2004;40:774-782.).
Physician-Assisted Suicide and Euthanasia in Washington State
Authors: Anthony L. Back
Journal: JAMA (1996)

<h3>Objectives.</h3> —To estimate how often physicians receive requests for physician-assisted suicide and euthanasia and to describe a case series of patient requests for physician-assisted suicide and euthanasia, including physician responses to these requests. <h3>Design.</h3> —A mailed, anonymous two-part questionnaire. <h3>Participants.</h3> —A total of 828 physicians returned questionnaires sent to 1453 potential respondents, for a response rate of 57%. Questionnaires were mailed to a random sample (25%) of primary care physicians and all physicians in selected medical subspecialties in Washington State. <h3>Main Outcome Measures.</h3> —The frequency of explicit patient requests for physician-assisted suicide and euthanasia reported by physicians and individual case descriptions of patient characteristics, physician perceptions of patient concerns, and physician responses to patient requests. <h3>Results.</h3> —In the past year, 12% of responding physicians received one or more explicit requests for physician-assisted suicide, and 4% received one or more requests for euthanasia. These physicians provided 207 case descriptions. The diagnoses most often associated with requests were cancer, neurological disease, and the acquired immunodeficiency syndrome (AIDS). The patient concerns most often perceived by physicians were worries about loss of control, being a burden, being dependent on others for personal care, and loss of dignity. Physicians provided assistance more often to patients with physical symptoms. Physicians infrequently sought advice from colleagues. Of 156 patients who requested physician-assisted suicide, 38 (24%) received prescriptions, and 21 of these died as a result. Of 58 patients who requested euthanasia, 14 (24%) received parenteral medication and died. <h3>Conclusions.</h3> —Patient requests for physician-assisted suicide and euthanasia are not rare. As perceived by physicians, the most common patient concerns at the time these requests are made are nonphysical. Physicians occasionally provide these practices, even though they are currently illegal in Washington State. Physicians do not consult colleagues often about these requests. These findings raise the question of how to ensure quality in the evaluation of patient requests for physician-assisted death. (<i>JAMA</i>. 1996;275:919-925)
Peritoneal Dialysis in the 21st Century
Authors: Catherine M. Hoff, Ty R. Shockley
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. One of the greatest biotechnologic advances of the last 25 yr is genetic engineering—the ability to identify and isolate individual genes and transfer genetic elements between cells. Genetic engineering forms the basis of a unique biotechnology platform called gene therapy: an approach to treating disease through genetic manipulation. It is becoming clear that during peritoneal dialysis, the peritoneal membrane undergoes various structural and functional changes that compromise the dialyzing efficiency of the membrane and eventually lead to membrane failure. A gene therapy strategy based on genetic modification of the peritoneal membrane could improve the practice of peritoneal dialysis through the production of proteins that would be of therapeutic value in preventing membrane damage and preserving its dialyzing capacity. The peritoneal membrane can be genetically modified by either ex vivo or in vivo gene transfer strategies with a variety of potentially therapeutic genes, including those for anti-inflammatory cytokines, fibrinolytic factors, and antifibrotic molecules. These genes could be administered either on an acute basis, such as in response to peritonitis, or on an intermittent basis to maintain physiologic homeostasis and perhaps to prevent the adverse changes in the membrane that occur over time. The anticipated effect of a gene therapy strategy could be measured in maintenance of desired transport characteristics and in patients being able to remain on the therapy for longer periods of time without the negative outcomes. In summary, the use of a gene therapy strategy to enhance peritoneal dialysis is an innovative and exciting concept with the potential to provide new treatment platforms for patients with end-stage renal disease.
Burkitt Lymphoma in a Patient With Neurofibromatosis and Pheochromocytoma
Authors: Brian W. Berman
Journal: JAMA (1977)

MULTIPLICITY of tumors is being recognized with increasing frequency. The association of pheochromocytoma with Recklinghausen neurofibromatosis is a well-known but infrequent phenomenon. To the best of our knowledge, neither has been reported as occurring together with Burkitt lymphoma. We report the unusual occurrence of Burkitt lymphoma, pheochromocytoma, and Recklinghausen neurofibromatosis in a single person and comment on possible interrelationships. <h3>Report of a Case</h3> In July 1973, a 20-year-old woman underwent curetting of a mass growing at the site of a prior dental extraction. Histologic examination suggested an anaplastic malignant process. In the course of her evaluation, multiple cafe-au-lait spots were noted on the trunk and extremities along with numerous 0.5-cm, spongy, subcutaneous nodules on the abdomen and lower back. Findings from a bone marrow aspiration and biopsy were compatible with iron deficiency anemia. Over the next two months, an expanding mass, which was lytic on roentgenograms, developed in the posterior
Letter to the Editor: Influence of maternal NAFLD on infant weight—the real precursor to NAFLD in offspring?
Authors: Monika Sarkar, Jennifer A. Flemming
Journal: Hepatology (2023)

To the editor, We read with enthusiasm the publication by Amadou et al.1 demonstrating that within a large French cohort, extremes of birthweight increased the risk for NAFLD in adulthood. On mediation analysis, findings for low birthweight were explained by prematurity. As the authors' highlight, an important limitation was unavailable maternal data, including maternal weight. Beyond maternal obesity, there remains a knowledge gap regarding the in-utero influence of maternal NAFLD on infant outcomes. NAFLD rates in pregnancy have nearly tripled over the past decade, and NAFLD cirrhosis is also rising in pregnant women.2,3 In pediatric populations, NAFLD can develop even in utero, and by school-age 10% of all children, and 30%–40% of those with obesity have NAFLD.4 Thus, there is an urgent need to identify early and modifiable risk factors in pregnant women with NAFLD and their offspring. Though prior data link maternal obesity to childhood NAFLD, the influence of maternal NAFLD on long-term metabolic outcomes has not been elucidated. In a large US study we evaluated NAFLD in pregnancy and maternal and perinatal outcomes at delivery.2 Importantly, maternal NAFLD increased risk for both large-for-gestational age infants (adjusted OR of 1.8, 95% CI: 1.4–2.5) and preterm birth (adjusted OR: 1.60, 95% CI: 1.3–2.0), independent of maternal metabolic comorbidities. Likewise, in our Canadian study of cirrhosis in pregnancy, maternal NAFLD independently increased arge-for-gestational age risk as compared with other etiologies of cirrhosis (RR: 1.6, 95% CI: 1.3–2.1).3 These data suggest a direct influence of in utero NAFLD exposure as a contributor to prematurity and arge-for-gestational age infants, key risk factors for long-term NAFLD risk in offspring as demonstrated by Amoudou and colleagues. Although the underlying mechanisms have not been elucidated, independent of diabetes and obesity the liver plays a critical role in the regulation of glucose and lipid metabolism. NAFLD-specific effects beyond the liver include peripheral insulin resistance, systemic inflammation, and dysregulated lipid metabolism, which may help to explain our findings of increased arge-for-gestational age risk in infants of mothers with NAFLD. In summary, we applaud the work by Amadou and colleagues and emerging literature evaluating early influencers of NAFLD. An even earlier focus on preconception through postpartum periods may further define contributors to NAFLD in offspring, and support interventions among expectant mothers to help mitigate rising NAFLD rates in young populations.
Publisher Correction: Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results
Authors: Sham Mailankody, Jeffrey V. Matous, Saurabh Chhabra, Michaela Liedtke, Surbhi Sidana, Olalekan O. Oluwole, Shahbaz Malik, Rajneesh Nath, Faiz Anwer, Jose Carlos Cruz, Myo Htut, Erin E. Karski, Wade Lovelace, Myles Dillon, Eric Butz, Wendy Ying, Arun Balakumaran, Shaji K. Kumar
Journal: Nature Medicine (2023)
Author Correction: Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial
Authors: Hatem Soliman, Deanna Hogue, Hyo Han, Blaise Mooney, Ricardo Costa, Marie C. Lee, Bethany Niell, Angela Williams, Alec Chau, Shannon Falcon, Aixa Soyano, Avan Armaghani, Nazanin Khakpour, Robert J. Weinfurtner, Susan Hoover, John Kiluk, Christine Laronga, Marilin Rosa, Hung Khong, Brian Czerniecki
Journal: Nature Medicine (2023)
SMO-CRISPR-mediated apoptosis in CD133-targeted cancer stem cells and tumor growth inhibition
Authors: Shambhavi Pandey, Myungchul Lee, Jaewoon Lim, Sangbae Park, Yun-Hoon Choung, Jae Eun Kim, Pankaj Garg, Jong Hoon Chung
Journal: Journal of Controlled Release (2023)
Meta-analysis of erosive hand osteoarthritis identifies four common variants that associate with relatively large effect
Authors: Unnur Styrkarsdottir, Lilja Stefansdottir, Gudmar Thorleifsson, Olafur A Stefansson, Saedis Saevarsdottir, Sigrun H Lund, Thorunn Rafnar, Kazuyuki Hoshijima, Kendra Novak, Natividad Oreiro, Ignacio Rego-Perez, Channing Hansen, Nikolas Kazmers, Lambertus A Kiemeney, Francisco J Blanco, Tyler Barker, Margreet Kloppenburg, Michael J Jurynec, Daniel F Gudbjartsson, Helgi Jonsson, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Annals of the Rheumatic Diseases (2023)

Objectives Erosive hand osteoarthritis (EHOA) is a severe subset of hand osteoarthritis (OA). It is unclear if EHOA is genetically different from other forms of OA. Sequence variants at ten loci have been associated with hand OA but none with EHOA. Methods We performed meta-analysis of EHOA in 1484 cases and 550 680 controls, from 5 populations. To identify causal genes, we performed eQTL and plasma pQTL analyses, and developed one zebrafish mutant. We analysed associations of variants with other traits and estimated shared genetics between EHOA and other traits. Results Four common sequence variants associated with EHOA, all with relatively high effect. Rs17013495 ( SPP1 / MEPE , OR=1.40, p=8.4×10 −14 ) and rs11243284 (6p24.3, OR=1.35, p=4.2×10 −11 ) have not been associated with OA, whereas rs11631127 ( ALDH1A2 , OR=1.46, p=7.1×10 −18 ), and rs1800801 ( MGP , OR=1.37, p=3.6×10 −13 ) have previously been associated with hand OA. The association of rs1800801 ( MGP ) was consistent with a recessive mode of inheritance in contrast to its additive association with hand OA (OR homozygotes vs non-carriers=2.01, 95% CI 1.71 to 2.37). All four variants associated nominally with finger OA, although with substantially lower effect. We found shared genetic components between EHOA and other OA measures, grip strength, urate levels and gout, but not rheumatoid arthritis. We identified ALDH1A2 , MGP and BMP6 as causal genes for EHOA, with loss-of-function Bmp6 zebrafish mutants displaying EHOA-like phenotypes. Conclusions We report on significant genetic associations with EHOA. The results support the view of EHOA as a form of severe hand OA and partly separate it from OA in larger joints.